2024
Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children
Goodwin J, Kajubi R, Wang K, Li F, Wade M, Orukan F, Huang L, Whalen M, Aweeka F, Mwebaza N, Parikh S. Persistent and multiclonal malaria parasite dynamics despite extended artemether-lumefantrine treatment in children. Nature Communications 2024, 15: 3817. PMID: 38714692, PMCID: PMC11076639, DOI: 10.1038/s41467-024-48210-7.Peer-Reviewed Original ResearchConceptsDay 7 lumefantrine concentrationsArtemether-lumefantrine treatmentRing-stage parasitesEarly post-treatmentEarly post-treatment periodArtemether-lumefantrineArtemisinin resistanceDay regimenMulticlonal infectionsEfficacious therapyFollow-upRandomized trialsPersistent clonesTransmission settingsEffective treatmentPost-treatment periodRegimensAntimalarial studiesStandard diagnosticsStandard 3DaysPost-treatmentChildrenTreatmentTherapy
2022
Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda
Kay K, Goodwin J, Ehrlich H, Ou J, Freeman T, Wang K, Li F, Wade M, French J, Huang L, Aweeka F, Mwebaza N, Kajubi R, Riggs M, Ruiz‐Garcia A, Parikh S. Impact of Drug Exposure on Resistance Selection Following Artemether‐Lumefantrine Treatment for Malaria in Children With and Without HIV in Uganda. Clinical Pharmacology & Therapeutics 2022, 113: 660-669. PMID: 36260349, PMCID: PMC9981240, DOI: 10.1002/cpt.2768.Peer-Reviewed Original ResearchConceptsLopinavir-ritonavirLumefantrine concentrationsSensitive parasitesRecurrence riskPopulation PK/PD modelArtemether-lumefantrine treatmentTrimethoprim-sulfamethoxazole prophylaxisPK/PD modelPopulation PK modelFirst-order absorptionHigh transmission regionsAntiretroviral regimensLumefantrine exposureLumefantrine susceptibilityPfcrt K76Pfmdr1 N86Suboptimal dosingArtemether-lumefantrineTwo-compartment modelHIV statusRecurrent infectionsCombination therapyDrug exposurePrimary treatmentArtemisinin resistanceThe Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial
Whalen ME, Kajubi R, Goodwin J, Orukan F, Colt M, Huang L, Richards K, Wang K, Li F, Mwebaza N, Aweeka FT, Parikh S. The Impact of Extended Treatment With Artemether-lumefantrine on Antimalarial Exposure and Reinfection Risks in Ugandan Children With Uncomplicated Malaria: A Randomized Controlled Trial. Clinical Infectious Diseases 2022, 76: 443-452. PMID: 36130191, PMCID: PMC9907485, DOI: 10.1093/cid/ciac783.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrineReinfection riskArtemisinin-based combination therapyDay 7 levelsOverall drug exposureHigh transmission settingsYoung childrenAntimalarial exposureUncomplicated malariaExtended regimenRecurrent parasitemiaControlled TrialsPrimary outcomeCombination therapyKaplan-MeierDrug exposureTotal episodesUgandan childrenArtemisinin resistanceLumefantrine concentrationsPharmacodynamic studiesHigh riskPharmacokinetic parametersRecurrence riskDay 7
2016
Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children
Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Antiretroviral Choice for HIV Impacts Antimalarial Exposure and Treatment Outcomes in Ugandan Children. Clinical Infectious Diseases 2016, 63: 414-422. PMID: 27143666, PMCID: PMC4946019, DOI: 10.1093/cid/ciw291.Peer-Reviewed Original ResearchConceptsArtemether-lumefantrine treatmentLPV/rRecurrent malariaLumefantrine exposureDrug exposureCritical drug-drug interactionsFirst-line antiretroviral therapy regimensArtemisinin-based combination therapyLopinavir/ritonavirAntiretroviral therapy regimensPlasmodium falciparum malariaHuman immunodeficiency virusDay 7 concentrationsMalaria-endemic regionsDrug-drug interactionsAntimalarial exposureAntimalarial componentPharmacokinetic samplingArtemether-lumefantrineFalciparum malariaClinical outcomesDosing regimensTherapy regimensImmunodeficiency virusCombination therapy